Collaborative transfection experiments have defined the contribution of altered expression levels for several genes to breast cancer metastatic progression. Such experiments have included the c-erb-B-2 (Her-2/neu) oncogene, which caused a 2-5 fold increase in spontaneous metastatic potential. We have previously transfected the cDNA encoding the extracellular matrix component thrombospondin into MDA-MB-435 breast carcinoma cells, and observed smaller primary tumor formation and decreased metastatic potential in vivo, concomitant with reduced capillary densities, suggestive of an anti-angiogenic effect. Site directed mutants of thrombospondin have been produced and are being evaluated for in vivo tumorigenicity and metastatic potential, in order to define the functional domains of this protein. In collaboration with Dr. Fuqua, the hsp27 heat shock protein has been transfected into MDA-MB-435 and MDA-MB-231 breast carcinoma cells, and the in vitro and in vivo phenotypes of the transfectants are under investigation. In vitro motility of the hsp27 transfectants was decreased to a variety of stimuli.